: A new type of instrument for in vivo histopathologic examination is proposed. The instrument combines the basic elements of a laser-scanning confocal microscope with a fiber-optic image bundle, allowing imaging of tissues only accessible by an optical catheter while maintaining the depth discrimination, or optical sectioning, of the confocal microscope. This provides the potential for in situ histopathologic examination of living tissues. There are three components to the proposed research: The first is system development to make a viable clinical instrument. This involves continued development of a slit-scan confocal microscope, imaging optics and focusing mechanism at the distal end of the fiber- optic catheter, and inclusion of a standard endoscopic imaging system for catheter guidance. The second component is evaluation of the confocal imaging system in terms of lateral resolution, axial resolution, radiometric efficiency, signal-to-noise ratio, and stability. The third component is to show the potential of this instrument for in vivo histopathologic examination. The system will be tested first in a tissue model consisting of ovarian cancer cells grown on a layer of fibroblasts, then in organ culture from a SCID mouse model of human ovarian cancer, and finally in vivo in the anesthetized animal. Reflection imaging, imaging of tissue auto-Fluorescence, and vital staining combined with fluorescence imaging will be investigated. The successful development of this optical biopsy instrument may provide a new tool for cancer diagnosis, leading to improved accuracy and improved efficiency of the diagnostic examination.